Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was to evaluate the GeneXpert MRSA/SA SSTI Assay (Xpert MRSA/SA) (Cepheid, Sunnyvale, CA) for use in lower respiratory tract (LRT) specimens for rapid MRSA detection and to determine the potentially saved antibiotic-days if a culture-based identification method was replaced by this assay. Remnant LRT samples from ventilated patients submitted to the microbiology laboratory for routine culture were tested using conventional culture and Xpert MRSA/SA. One hundred of 310 LRT specimens met the inclusion criteria. Ten samples were positive for MRSA by Xpert MRSA/SA, while six were positive by routine culture methods. Xpert MRSA/SA correctly identified 5/6 positive and 89/94 negative MRSA specimens, for a sensitivity of 83.3%, specificity of 94.7%, positive predictive value of 45.6%, and negative predictive value of 98.9%. The assay also correctly detected 3/3 positive and 90/97 negative methicillin-susceptible S. aureus (MSSA) specimens, for a sensitivity of 100%, specificity of 92.8%, positive predictive value of 30%, and negative predictive value of 100%. A total of 748 vancomycin and 305 linezolid antibiotic-days were associated with the enrolled specimens. Vancomycin and linezolid utilization could decrease by 68.4% and 83%, respectively, if discontinued 1 day after negative polymerase chain reaction (PCR) results. The Xpert MRSA/SA SSTI rapid MRSA PCR assay performed well in respiratory samples from ventilated patients with suspected pneumonia and has the potential to facilitate stewardship efforts such as reducing empiric vancomycin and linezolid therapy.

Antibiotic management of ventilator-associated pneumonia due to antibiotic-resistant gram-positive bacterial infection.

Gram-positive cocci, in particular Staphylococcus aureus, account for as much as one-third of all cases of hospital-acquired pneumonia, and treatment has become increasingly complex as the proportion of resistant isolates has increased. Methicillin-resistant S. aureus is of particular concern because this pathogen is now associated with hospital-acquired, ventilator-associated, community-acquired, and healthcare-associated pneumonia. Antibiotic therapy for ventilator-associated pneumonia is challenging because it can be caused by multiple pathogens, which can be resistant to multiple drugs. This article reviews the epidemiology of ventilator-associated pneumonia and describes options for antibiotic treatment. Particular attention is paid to pneumonia due to methicillin-resistant S. aureus. Studies suggest that vancomycin, the traditional treatment for ventilator-associated pneumonia, may not be the best option for this type of pneumonia and that other antibiotics, such as linezolid and clindamycin, might be better choices. New antibiotics with activity against methicillin-resistant S. aureus are under investigation and may soon become available for clinical use. Studies are needed to define the optimal choice of antibiotic for pneumonias caused by this organism, and these choices will need to be balanced with the need to minimize the emergence of resistance.

Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines.

Health-care professionals (HCPs) can provide protocol-based care that has a measurable impact on critically ill patients beyond their liberation from mechanical ventilation (MV). Randomized controlled trials have demonstrated that protocols for liberating patients from MV driven by nonphysician HCPs can reduce the duration of MV. The structure and features of protocols should be adapted from published protocols to incorporate patient-specific needs, clinician preferences, and institutional resources. As a general approach, shortly after patients demonstrate that their condition has been stabilized on the ventilator, a spontaneous breathing trial (SBT) is safe to perform and is indicated. Ventilator management strategies for patients who fail a trial of spontaneous breathing include the following: (1) consideration of all remediable factors (such as electrolyte derangements, bronchospasm, malnutrition, patient positioning, and excess secretions) to enhance the prospects of successful liberation from MV; (2) use of a comfortable, safe, and well-monitored mode of MV (such as pressure support ventilation); and (3) repeating a trial of spontaneous breathing on the following day. For patients who pass the SBT, the decision to extubate must be guided by clinical judgment and objective data to minimize the risk of unnecessary reintubations and self-extubations. Protocols should not represent rigid rules but, rather, guides to patient care. Moreover, the protocols may evolve over time as clinical and institutional experience with them increases. Useful protocols aim to safely and efficiently liberate patients from MV, reducing unnecessary or harmful variations in approach.

Optimizing antibiotic therapy in the intensive care unit setting.

Antibiotics are one of the most common therapies administered in the intensive care unit setting. In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms. Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance. This review will present several strategies aimed at achieving optimal use of antimicrobial agents. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de-escalation therapy) be evaluated at the local level.

The occurrence of ventilator-associated pneumonia in a community hospital: risk factors and clinical outcomes.

STUDY OBJECTIVES: To prospectively identify the occurrence of ventilator-associated pneumonia (VAP) in a community hospital, and to determine the risk factors for VAP and the influence of VAP on patient outcomes in a nonteaching institution. DESIGN: Prospective cohort study. SETTING: A medical ICU and a surgical ICU in a 500-bed private community nonteaching hospital: Missouri Baptist Hospital. PATIENTS: Between March 1998 and December 1999, all patients receiving mechanical ventilation who were admitted to the ICU setting were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: During a 22-month period, 3,171 patients were admitted to the medical and surgical ICUs. Eight hundred eighty patients (27.8%) received mechanical ventilation. VAP developed in 132 patients (15.0%) receiving mechanical ventilation. Three hundred one patients (34.2%) who received mechanical ventilation died during hospitalization. Logistic regression analysis demonstrated that tracheostomy (adjusted odds ratio [AOR], 6.71; 95% confidence interval [CI], 3.91 to 11.50; p < 0.001), multiple central venous line insertions (AOR, 4.20; 95% CI, 2.72 to 6.48; p < 0.001), reintubation (AOR, 2.88; 95% CI, 1.78 to 4.66; p < 0.001), and the use of antacids (AOR, 2.81; 95% CI, 1.19 to 6.64; p = 0.019) were independently associated with the development of VAP. The hospital mortality of patients with VAP was significantly greater than the mortality of patients without VAP (45.5% vs 32.2%, respectively; p = 0.004). The occurrence of bacteremia, compromised immune system, higher APACHE (acute physiology and chronic health evaluation) II scores, and older age were identified as independent predictors of hospital mortality. CONCLUSIONS: These data suggest that VAP is a common nosocomial infection in the community hospital setting. The risk factors for the development of VAP and risk factors for hospital mortality in a community hospital are similar to those identified from university-affiliated hospitals. These risk factors can potentially be employed to develop local strategies for the prevention of VAP. CLINICAL IMPLICATIONS: ICU clinicians should be aware of the risk factors associated with the development of VAP and the impact of VAP on clinical outcomes. More importantly, they should cooperate in the development of local multidisciplinary strategies aimed at the prevention of VAP and other nosocomial infections.

Experience with a clinical guideline for the treatment of ventilator-associated pneumonia.

OBJECTIVE: To evaluate a clinical guideline for the treatment of ventilator-associated pneumonia. DESIGN: Prospective before-and-after study design. SETTING: A medical intensive care unit from a university-affiliated, urban teaching hospital. PATIENTS: Between April 1999 and January 2000, 102 patients were prospectively evaluated. INTERVENTIONS: Prospective patient surveillance, data collection, and implementation of an antimicrobial guideline for the treatment of ventilator-associated pneumonia. MEASUREMENTS AND MAIN RESULTS: The main outcome evaluated was the initial administration of adequate antimicrobial treatment as determined by respiratory tract cultures. Secondary outcomes evaluated included the duration of antimicrobial treatment for ventilator-associated pneumonia, hospital mortality, intensive care unit and hospital lengths of stay, and the occurrence of a second episode of ventilator-associated pneumonia. Fifty consecutive patients with ventilator-associated pneumonia were evaluated in the before period and 52 consecutive patients with ventilator-associated pneumonia were evaluated in the after period. Severity of illness using Acute Physiology and Chronic Health Evaluation II (25.8 +/- 5.7 vs. 25.4 +/- 8.1, p =.798) and the clinical pulmonary infection scores (6.6 +/- 1.0 vs. 6.9 +/- 1.2, p =.105) were similar for patients during the two treatment periods. The initial administration of adequate antimicrobial treatment was statistically greater during the after period compared with the before period (94.2% vs. 48.0%, p <.001). The duration of antimicrobial treatment was statistically shorter during the after period compared with the before period (8.6 +/- 5.1 days vs. 14.8 +/- 8.1 days, p <.001). A second episode of ventilator-associated pneumonia occurred statistically less often among patients in the after period (7.7% vs. 24.0%, p =.030). CONCLUSIONS: The application of a clinical guideline for the treatment of ventilator-associated pneumonia can increase the initial administration of adequate antimicrobial treatment and decrease the overall duration of antibiotic treatment. These findings suggest that similar types of guidelines employing local microbiological data can be used to improve overall antibiotic utilization for the treatment of ventilator-associated pneumonia.

Is there a role for antibiotic cycling in the intensive care unit?

Antibiotic resistance of bacterial pathogens has emerged as one of the most important issues facing critical care practitioners. Resistance of many commonly encountered bacterial species is increasing and has been associated with greater administration of inadequate antimicrobial therapy to patients within intensive care units. This has resulted in greater patient morbidity, higher mortality rates, and increased healthcare costs. Methods to reduce antimicrobial resistance have focused on increasing adherence to infection control practices and improving antibiotic utilization. Antibiotic cycling is a strategy to reduce antimicrobial resistance by withdrawing an antibiotic or antibiotic class from use and subsequently reintroducing it at a later point in time. The main goal of cycling is to allow resistance rates for specific antibiotics to decrease, or at least remain stable, when their use is periodically eliminated from the intensive care unit.

The impact of the introduction of a rapid D-dimer assay on the diagnostic evaluation of suspected pulmonary embolism.

BACKGROUND: Rapid D-dimer assays are being used in the diagnostic evaluation of suspected pulmonary embolism (PE). Although this hypothesis is anticipated to decrease the use of ventilation-perfusion (VQ) scans and other diagnostic tests for PE, it has not been tested in a "real-world" environment. SUBJECTS AND METHODS: A randomized prospective trial was conducted on 470 of the 5390 enrolled patients aged 60 years and older who had previously undergone any diagnostic tests for PE at an urban teaching hospital. The use of D-dimer as part of the diagnostic evaluation for PE was promulgated in the 2 randomly chosen intervention firms. The remaining 2 firms served as controls. MAIN OUTCOME MEASURES: The number of VQ scans, spiral computed tomographic scans, and pulmonary angiograms performed. Secondary outcomes included mortality and thromboembolic or bleeding events during 3 months of follow-up. RESULTS: Of the 470 inpatients who underwent evaluation for PE on a per PE workup basis, fewer VQ scans were performed in the intervention firms (63.8% vs 81.3%; P<.01). However, the number of patients evaluated for PE nearly doubled in the intervention firms (304 vs 166; P<.01), so that more VQ scans were performed in the intervention than in the control firms (194 vs 135; P<.01). Ninety-four patients from the control firms and 160 patients from the intervention firms were diagnosed and treated for venous thromboembolic disease (P<.01). There were no differences in secondary outcomes during the 3-month follow-up. CONCLUSIONS: The introduction of a rapid D-dimer assay increased the number of VQ scans performed because the number of patients screened for PE increased. A larger number of patients in the intervention firms were diagnosed as having venous thromboembolic disease (PE and/or deep vein thrombosis). There were no perceived changes in mortality or venous thromboembolic events during the 3-month follow-up.

Antibiotic resistance in the intensive care unit.

Antimicrobial resistance has emerged as an important determinant of outcome for patients in the intensive care unit (ICU). This is largely due to the administration of inadequate antimicrobial treatment, which is most often related to bacterial antibiotic resistance. In addition, the escalating problem of antimicrobial resistance has substantially increased overall health care costs. This increase is a result of prolonged hospitalizations and convalescence associated with antibiotic treatment failures, the need to develop new antimicrobial agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens. Intensive care units are unique because they house seriously ill patients in confined environments where antibiotic use is extremely common. They have been focal points for the emergence and spread of antibiotic-resistant pathogens. Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices. Clinicians caring for critically ill patients should consider antimicrobial resistance as part of their routine treatment plans. Careful, focused attention to this problem at the local ICU level, using a multidisciplinary approach, will have the greatest likelihood of limiting the development and dissemination of antibiotic-resistant infections.

Using protocols to improve the outcomes of mechanically ventilated patients. Focus on weaning and sedation.

The use of nonphysician-directed protocols and guidelines for the management of sedation and weaning has been shown to reduce the duration of mechanical ventilation for patients with acute respiratory failure when compared with conventional physician-directed practices. Practitioners in ICUs frequently are needed to perform multiple tasks and to evaluate numerous elements of clinical information in the care of the critically ill. In this complex environment, protocols and guidelines are one strategy for ensuring that specific tasks are carried out in a timely manner. Simple-to-employ methods for facilitating changes and improvements in the care of hospitalized patients recently have been proposed. These methods emphasize the importance of developing a culture of cooperation within the ICU so protocols and guidelines can be implemented successfully. Such a culture should embrace changes in medical practices in the ICU if they are associated with improved clinical outcomes. The results of studies evaluating the use of protocols and guidelines have important implications for general critical care practices, because many ICUs do not have physicians who are constantly at the patient's bedside. The need for effective communication from the bedside caregiver (e.g., nurse, respiratory therapist, pharmacist, technician) to the physician, so that treatment orders can be changed appropriately, usually results in some delay in the implementation of treatment changes. Protocols are one method for potentially reducing those delays and ensuring that medical care is administered in a more standardized and efficient manner.

Ventilator-associated pneumonia complicating the acute respiratory distress syndrome.

Pulmonary infections span a wide spectrum, ranging from self-limited processes (e.g., tracheobronchitis) to life-threatening infections including both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Together, pneumonia and influenza rank as the sixth leading cause of death in the United States and lead all other infectious diseases in this respect. Pneumonia is the second-most-common hospital-acquired infection in the United States, accounting for 17.8% of all hospital-acquired infections and 40,000 to 70,000 deaths per year. HAP is the most common nosocomial infection occurring in patients requiring mechanical ventilation, developing in 6.5% of patients after 10 days and in 28% of patients after 30 days of ventilatory support. Patients acquiring HAP have a greater risk of mortality than comparably ill ventilated patients who do not develop pneumonia. Ventilator-associated pneumonia (VAP) specifically refers to a bacterial pneumonia developing in patients with acute respiratory failure who have been receiving mechanical ventilation for at least 48 hours. The etiologic bacteriologic agents associated with VAP typically differ based on the timing of the occurrence of the infection relative to the start of mechanical ventilation. VAP occurring within 96 hours of the onset of mechanical ventilation is usually due to antibiotic-sensitive bacteria that colonize the patient prior to hospital admission (e.g., Streptococcus pneumoniae, Haemophilus influenza, oxacillin-sensitive Staphylococcus aureus). VAP developing after 96 hours of ventilatory support is more often associated with antibiotic-resistant bacteria including oxacillin-resistant Staphylococcus aureus, Acinetobacter species and Pseudomonas aeruginosa. However, more recent data suggest that hospitalization and exposure to antibiotics prior to the start of mechanical ventilation are important risk factors for the occurrence of VAP attributed to antibiotic-resistant bacteria. Therefore, these risk factors should be considered when deciding on an appropriate empiric antibiotic regimen regardless of the onset of VAP. VAP and catheter-associated bloodstream infections are the leading causes of infection acquired in the intensive care unit (ICU) setting. Patients in the ICU have rates of HAP that are as much as five to ten times higher than the rates in general hospital wards. Additionally, like nosocomial bloodstream infections, VAP is associated with an attributable mortality beyond that accounted for by patients' severity of illness. The attributable mortality associated with VAP appears to be greatest for "high-risk'' antibiotic-resistant bacteria including Pseudomonas aeruginosa and oxacillin-resistant Staphylococcus aureus. The greater hospital mortality associated with these "high-risk'' pathogens has been attributed to the virulence of these bacteria and the increased occurrence of inadequate initial antibiotic treatment of VAP due to the presence of antibiotic resistance. This review provides an overview of the clinical importance of VAP. We then describe how this nosocomial infection influences the management and outcomes of patients with the acute respiratory distress syndrome (ARDS).

Opinion: the clinical use of selective digestive decontamination.

Several recent meta-analyses have shown that the use of SDD can reduce the occurrence of nosocomial pneumonia among ventilated patients in the intensive care unit (ICU) setting. However, the use of SDD has also been demonstrated to increase subsequent patient colonization and infection with antibiotic-resistant bacteria, particularly Gram-positive cocci. Therefore, the routine use of SDD cannot be advocated at the present time. The mortality benefit of SDD appears to occur in surgical/trauma patients, and to be associated primarily with the administration of parenteral antibiotics. This is already an accepted practice in most patients during the perioperative period (eg prophylactic parenteral antibiotics for 24 h). Prolonged decontamination of the aerodigestive tract with topical antimicrobials does not appear to influence outcome, and should not be routinely employed.

Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices.

OBJECTIVE: The purpose of this study was to determine the impact of scheduled changes of antibiotic classes, used for the empirical treatment of suspected or documented Gram-negative bacterial infections, on the occurrence of inadequate antimicrobial treatment of nosocomial infections. DESIGN: Prospective observational study. SETTING: Medical (19-bed) and surgical (18-bed) intensive care units in an urban teaching hospital. PATIENTS: A total of 3,668 patients requiring intensive care unit admission were prospectively evaluated during three consecutive time periods. INTERVENTIONS: During each time period, one antibiotic class was selected for the empirical treatment of Gram-negative bacterial infections as follows: time period 1 (baseline period) (1,323 patients), ceftazidime; time period 2 (1,243 patients), ciprofloxacin; and time period 3 (1,102 patients), cefepime. MEASUREMENTS AND MAIN RESULTS: The overall administration of inadequate antimicrobial treatment for nosocomial infections decreased during the course of the study (6.1%, 4.7%, and 4.5%; p = .15). This was primarily because of a statistically significant decrease in the administration of inadequate antibiotic treatment for Gram-negative bacterial infections (4.4%, 2.1%, and 1.6%; p < .001). There were no statistically significant differences in the overall hospital mortality rate among the three time periods (15.6%, 16.4%, and 16.2%; p = .828) despite a significant increase in severity of illness as measured with Acute Physiology and Chronic Health Evaluation (APACHE) II scores (15.3 +/- 7.6, 15.7 +/- 8.0, and 20.7 +/- 8.6; p < .001). The hospital mortality rate decreased significantly during time period 3 (20.6%) compared with time period 1 (28.4%; p < .001) and time period 2 (29.5%; p < .001) for patients with an APACHE II score > or = 15. CONCLUSIONS: These data suggest that scheduled changes of antibiotic classes for the empirical treatment of Gram-negative bacterial infections can reduce the occurrence of inadequate antibiotic treatment for nosocomial infections. Reducing inadequate antibiotic administration may improve the outcomes of critically ill patients with APACHE II scores > or = 15.

Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients.

Inadequate antimicrobial treatment, generally defined as microbiological documentation of an infection that is not being effectively treated, is an important factor in the emergence of infections due to antibiotic-resistant bacteria. Factors that contribute to inadequate antimicrobial treatment of hospitalized patients include prior antibiotic exposure, use of broad-spectrum antibiotics, prolonged length of stay, prolonged mechanical ventilation, and presence of invasive devices. Strategies to minimize inadequate treatment include consulting an infectious disease specialist, using antibiotic practice guidelines, and identifying quicker methods of microbiological identification. In addition, clinicians should determine the prevailing pathogens that account for the community-acquired and nosocomial infections identified in their hospitals. Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles. This broad-spectrum therapy can then be narrowed when initial culture results are received. Further study evaluating the use of antibiotic practice guidelines and strategies to reduce inadequate treatment is necessary to determine their impact on patient outcomes.

Early versus late tracheostomy in patients who require prolonged mechanical ventilation.

OBJECTIVES: To compare the clinical outcomes of early versus late tracheostomy in patients who require prolonged mechanical ventilation. METHODS: A prospective observational study was done. The sample was a cohort of 90 patients who had tracheostomy in the medical intensive care unit of a university-affiliated teaching hospital. Primary outcome measures were duration of mechanical ventilation and total cost of hospitalization. Tracheostomy was defined as early if performed by day 10 of mechanical ventilation and late if performed thereafter. RESULTS: Fifty-three patients had early tracheostomy (mean +/- SD = day 5.9 +/- 7.2 of ventilation), and 37 patients had late tracheostomy (mean +/- SD = day 16.7 +/- 2.9) (P < .001). The mean (+/- SD) duration of mechanical ventilation was 28.3 +/- 28.2 days in the early-tracheostomy group versus 34.4 +/- 17.8 days in the late-tracheostomy group (P = .005). Total cost of hospitalization was significantly lower in the early-tracheostomy group (mean +/- SD = $86,189 +/- $53,570) than in the late-tracheostomy group (mean +/- SD = $124,649 +/- $54,282) (P = .001). Male sex (adjusted odds ratio = 3.84; 95% CI = 2.32-6.34; P = .007) and higher ratios of PaO2 to fraction of inspired oxygen (adjusted odds ratio = 1.01; 95% CI = 1.00-1.01; P = .03) were associated with early tracheostomy. The timing of tracheostomy was not associated with hospital mortality. CONCLUSION: Early tracheostomy is associated with shorter lengths of stay and lower hospital costs than is late tracheostomy among patients in the medical intensive care unit. Prospective clinical trials are necessary to determine the optimal timing of tracheostomy in that setting.